The first use of a substance frequently fixes, for a time, its purpose, dose, or method of use. That was the case with papaverine, used for decades in about 30-mg doses—too small to be effective. The situation was similar with nicotinic acid.

Though used by Spies in the late 1930's to reverse the mental changes in pellagra, the image of nicotonic acid became substantially that of a vitamin—given in doses of 10-15 mg a day—to prevent deficiency symptoms. It was also administered in daily doses of 25-50 mg, occasionally in 100 mg doses per day. The mental stereotype of milligram doses of that order of magnitude became fixed. Perhaps this accounted for the resistance to the use of nicotinic acid in depressing blood cholesterol levels, as described by Altschul and Hoffer in 1955. They used doses of 3 gm a day—at times up to 10 gm(!) per day. Others had